The general objective of this program is to synthesize antagonists of the luteinizing hormone-releasing hormone (LH-RH) capable of preventing ovulation. Antagonistic analogs will be so devised that steric, conformational and electronic similarities to LH-RH will be preserved in order to attain recognition by the pituitary hormone receptor, but they will lack the features necessary to elicit the normal response. Antagonists resistant to enzymatic degradation will be prepared as a means of prolonging their duration of action thus leading to orally active antiovulatory agents. The effects of these analogs on LH and FSH release will be measured by bioassays, radioimmunoassays, as well as by their ability to inhibit ovulation in intact animals. Hormone-receptor interactions in relation to Structure Activity Relationship will be evaluated by means of binding with cell receptors and adenylate cyclase activation studies in pituitary cell-free preparations. Another important facet of this study will be the the investigation of the conformation of LH-RH in solution, which will be valuable to ascertain the steric, conformational and electronic requirements of the hormone-receptor interaction. The final facet of this study will involve testing the working hypothesis that transition metals are involved in the interaction between LH-RH and its receptors.